Manufacture of arylacetonitrile derivatives



Patented Aug. 14, 1945 MANUFACTURE or amrmcs'rom'rnma a nnarva'rrvasFranz'Bergel, Nathan Chadwick Hlndley, alerantler Lang Morrison, andHeinrich Binder- .knecht, Welwyn Garden City, England, assignors toRoche Products Limited, Wclwyn Garden City, England No Drawing.Application October 15, 1042, Serial 4 Claims.

where R'is an aryl group, which'may carry substituents not interferingwith the reaction, and X and Y are p-hydroxyalkyl groups.

The process of the present invention comprises condensing anarylacetonitrile possessing a reactive methylene group, such as benzylcyanide,

in the presence of an alkaline condensing reagent, capable of formingan,alkali derivative of the arylacetonitrile such as sodamide, withslightly more than two molecular proportions of a formal of thefollowing general formula:

where X is a halogen, n is two and m is zero or an integer andsubjecting the condensation prodnot to mild hydrolysis under acidconditions.

Formals of this type can be prepared by reactingw-halogen-alkyl-chloromethyl ethers with- In Great Britain November 19,5

alcohols'or their sodium derivatives as described by Henry (Ben, 1893,26, ref. 933; 1895, 28, ref. 857). We have, prepared, in a speciallyadvantageous manner, 5 chloro-ethylalkylformals from ethylene oxide andchloromethylalkyi where R is an aryl group, n is two and m is zero or aninteger, on mild hydrolysis with an acid reagent yields thecorresponding club-biS-(F- hydroxyalkyl) -arylacetonitrile, twomolecules of formaldehyde and two molecules of alcohol crmcnnmon.Replacement of the hydroxyl groups of the said compounds by halogengroups and condensing the resulting am-bis-ip' halogenalkyl)-arylacetonitriles with primary amines will give bases such as4-aryl-piperidine-initrile as described in our co-pending applicationSer. N0. 433,340, filed March 4, 1942.

The following example illustrates how, the process of the presentinvention may be carried into eflect.

To 22 parts by weight of dry liquid ethylene oxide, 40 parts by weightof chloromethyl other are added drop by drop with shaking at --5 to --10C. The temperature of the mixture is then allowed to rise gradually to25 C. After twelve hours standing at this temperature the mixture iswashed with dilute sodium carbonate solution and dried over anhydrouspotassium carbonate. In subsequent fractional distillation the fractionboiling at -138 C. is collected, which is the p-chloroethylmethylformal.

To a mixture of 11.7 parts by weight of benzyl cyanide and 27 parts byweight of the fl-chloroethylmethylformal and 120 parts by volume of drytoluene, 7.8 parts by weight of powdered sodamide are added in severalportions. The

reaction mixture is stirred mechanically and the temperature kept at3040" C. when the addition of sodamide has been completed, the reactionmixture is slowly heated to the boilin point and refluxing continued for1% hours. After cooling water is added and the toluene layer isseparated' The toluene solution is washed with water and evaporated. Theresidue is distilled in high vacuo, when aza-bis-(pf-(methoxy-methyleneoury) -ethyl) phenylacetonitrile comes over at -160C./0.2 mm. as a yellow viscous oil.

A suspension of five parts by weight of aid-bis- (p'(methoxy-methoxyleneoxy) -ethyl)-phenyl- We claim:

i. A process for the manufacture of aid-b18- (p' hydroxy ethyl)phenylacetonitrile which comprises condensing benzyl cyanide withpchloroethylmethylformal in the presence of sodamide and subjecting thes-s-bis-(p'- (methoxymethyleneoxy) ethyl) phenylacetonitriie thusformed-to hydrolysis with hydrochloric acid to wherein X is halogen andm is selected from the group consisting of zero and integers, in. thepresence of an alkaline condensing agent selected from the groupconsisting of alkaline agents consisting oi alkali metal compoundscapable of re, acting with active methylene group to produce alkalimetal substitution, and subjecting the condensation product to mildhydrolysis under acid conditions.

3. A process for the manufacture of ll:fl'bis- (p'-hydroxyalkyl)-phenylacetonitriles of the gen- 'eral formula AlkyLOH C AlkyLOH assaaacwherein R is an group, which process comprlses condensing a benzylcyanide with slightly more than two molecular proportions of a formal ofthe general formula wherein x is halogen and m is selected from the agroup consisting of zero and integers, in the presence of an alkalinecondensing agent selected from the group consisting of alkaline agentsconsisting of alkali metal compounds capable of reacting with activemethylene groups toproduce alkali metal substitution, and subjecting thecondensation product to mild hydrolysis under acid conditions.

4. A process for the manufacture of arm-bis- (fi-hydroxysikyl)-arylacetonitriles oi the general formula r Y AlkyLOH n-c 0N AlkyLOHwherein R is an aryl group, which process comprises condensinganarylscetonitrile with slightly more than two molecular proportions of aformal of the general formula wherein X is halogen and m is selectedfrom the group consisting of zero and integers, in the presence ofsodamide, and subjecting the condensation product to mild hydrolysisunder acid conditions. I

FRANZ BERGEL.

NATHAN CHADWICK HINDLEY. ALmANnER LANG MORRISON. rmnmrcn RINDERKNECHT.

